title: Chitin modulates innate immune responses of keratinocytes.
abstract: BACKGROUND
  Chitin, after cellulose the second most abundant polysaccharide in nature, is an essential component of exoskeletons of crabs, shrimps and insects and protects these organisms from harsh conditions in their environment. Unexpectedly, chitin has been found to activate innate immune cells and to elicit murine airway inflammation. The skin represents the outer barrier of the human host defense and is in frequent contact with chitin-bearing organisms, such as house-dust mites or flies. The effects of chitin on keratinocytes, however, are poorly understood.
  
  
  RESULTS
  We hypothesized that chitin stimulates keratinocytes and thereby modulates the innate immune response of the skin. Here we show that chitin is bioactive on primary and immortalized keratinocytes by triggering production of pro-inflammatory cytokines and chemokines. Chitin stimulation further induced the expression of the Toll-like receptor (TLR) TLR4 on keratinocytes at mRNA and protein level. Chitin-induced effects were mainly abrogated when TLR2 was blocked, suggesting that TLR2 senses chitin on keratinocytes.
  
  
  CONCLUSIONS
  We speculate that chitin-bearing organisms modulate the innate immune response towards pathogens by upregulating secretion of cytokines and chemokines and expression of MyD88-associated TLRs, two major components of innate immunity. The clinical relevance of this mechanism remains to be defined.
authors.affiliation: Department of Dermatology and Allergy, Ludwig-Maximilian-University, Munich, Germany. barbara.koller@med.uni-muenchen.de
authors.forename: Barbara
authors.initials: B
authors.lastname: Koller
authors.forename: Alisa Sophie
authors.initials: AS
authors.lastname: Müller-Wiefel
authors.forename: Rudolph
authors.initials: R
authors.lastname: Rupec
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Korting
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
mesh_terms: D018929:Cell Culture Techniques; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D002686:Chitin / Q000494:pharmacology* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000502:physiology; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D002686:Chitin; D010105:Oxygenases; C114415:nitric oxide dioxygenase